title: Erythropoiesis-stimulating agents in chronic kidney disease: what have we learned in 25 years?
abstract: Since the pioneering studies by Eschbach et al in 1987, erythropoiesis-stimulating agents (ESAs) have become the mainstay of anemia therapy in chronic kidney disease (CKD) patients. The introduction of ESAs 25 years ago markedly improved the lives of many patients with CKD, who until then had severe, often transfusion-dependent anemia. However, randomized controlled trials demonstrate an increased risk for cardiovascular events such as stroke, thrombosis, and death at nearly normal hemoglobin concentrations and higher ESA doses in CKD. By contrast, kidney transplant recipients may represent a unique population of CKD patients who may benefit from ESA therapy. This review discusses potential mechanisms involving the erythropoietic and nonerythropoietic effects of ESA treatment and ESA resistance. Further research aimed at elucidating the causal pathways is strongly recommended. Given current knowledge, however, clinical practice should avoid disproportionately high dosages of ESAs to achieve recommended hemoglobin targets, particularly in those with significant cardiovascular morbidity or ESA resistance. The key to CKD anemia management will be individualization of the potential benefits of reducing blood transfusions and anemia-related symptoms against the risks of harm.
authors.affiliation: Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Buddhist Tzu Chi University, Taipei, Taiwan.
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yao-Ping
authors.initials: YP
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, and Immunology Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan. Electronic address: dctarng@vghtpe.gov.tw.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000740:Anemia / Q000188:drug therapy; D004920:Erythropoiesis / Q000187:drug effects; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*
chemical_list: D006397:Hematinics
keywords: anemia; chronic kidney disease; erythropoiesis-stimulating agents; erythropoietin; hemodialysis